This study will address several key questions concerning the mechanism and control of lymph formation in mammals. The hydraulic resistance of the initial lymphatic wall will be measured to test the hypothesis that the lymphatic endothelium can act as a flap-valve two-point micropressure recordings (Wiederhielm) will be used as indicators of flow across the wall when intraluminal pressure is artificially altered. A finding of a lower wall port the lymphatic suction hypothesis of lymph formation. This phase will be carried out using the lymphatics in the wing of an unanesthetized bat. Further studies will be carried out on these contractile initial lymphatics to determine the relative importance of mechanical factors (wall tension) and chemical mediators (norepinephrine, acetylcholine, histamine, 5-hydroxytryptamine and bradykinin) on the control of initial lymphatic activity as it relates to lymph formation. Wall tension will be controlled by intraluminal saline infusion and drugs will be applied by ionophoresis. Measurements will include intraluminal pressure, pulsatile pressure, contractile frequency, and wall curvature. In the last phase of the project, previous studies in bat wing will be repeated using the non-contractile initial lymphaticsof the rat mesentery. Evidence of lymphatic suction will be sought be measuring pressure gradients across the initial lymphatic wall and across the first valve between initial and collecting lymphatics. The study of directional bias in wall resistance will also be repeated. This experiment is necessary to counter criticisms that lymphatic suction is a mechanism unique to the contractile initial lymphatics of the bat wing. This study of lymph formation is part of a longer term objective to understand the role of the lymphatics in body fluid homeostasis and, in particular, their contribution to the creation and maintenance of negative interstitial fluid pressure. The lymphatics are one of the three "safety factors" against edema in the body, but almost nothing is known about the mechanism or control of lymph formation. As an aid to the animal studies, a 2-channel digital micropressure system with self-test and self-optimization features will be developed for use in measuring pressure gradients in the lymphatics and interstitium.